Cellular Uptake and Transport Characteristics of FL118 Derivatives in Caco-2 Cell Monolayers.

In the evaluation of the druggability of candidate compounds, it was vital to predict the oral bioavailability of compounds from apparent permeability (Papp) across Caco-2 cell-culture model of intestinal epithelium cultured on commercial transwell plate inserts. The study was to investigate the transport characteristics and permeability of FL118 (10, 11-Methylenedioxy-20(S)-camptothecin) derivatives 7-Q6 (7-(4-Ethylphenyl)-10, 11-methylenedioxy-20(S)-camptothecin) and 7-Q20 (7-(4-Trifluoromethylphenyl)-10, 11-methylenedioxy-20(S)-camptothecin). Transport characteristics and permeability of the tested compounds to the small intestine were assessed at different concentrations (0.5, 1 µM) via Caco-2 cell monolayers model in vitro. Uptake studies based on Caco-2 cells, including temperatures, concentrations, and the influence of efflux transporters, were combined to confirm the transport characteristics of the tested compounds. Furthermore, cytotoxicity results showed that the concentrations used in the experiments were non-toxic and harmless to cells. In addition, The Papp of 7-Q6 was (3.69 ± 1.07) × 10-6 cm/s with efflux ratio (ER) 0.98, while the Papp of 7-Q20 was (7.78 ± 0.89) × 10-6 cm/s with ER 1.05 for apical-to-basolateral (AP→BL) at 0.5 µM, suggesting that 7-Q20 might possess higher oral bioavailability in vivo. Furthermore, P-glycoprotein (P-gp) was proved to slightly affect the accumulations of 7-Q20, while the absorption of 7-Q6 was irrelevant with P-gp and breast cancer resistant protein (BCRP) based on the cellular uptake assays. Accordingly, 7-Q6 was completely absorbed by passive diffusion, and 7-Q20 was mainly dependent on passive diffusion with being effluxed by P-gp slightly. Meanwhile, both 7-Q6 and 7-Q20 were potential antitumor drugs that might exhibit high oral bioavailability in the body.

Impact of landfill density on transport and hydraulic characteristics of recirculated leachate.

To achieve a uniform water distribution and to promote the stabilization of bioreactor landfills, the effects of different density on the transport and hydraulic characteristics of recirculated leachate were studied in a Li+ tracer experiment. The landfill density was related negatively to the maximum production rate of leachate, the percentage of Li+ tracer solution and the cumulative amount of Li+ that washed out in the first recirculation round. The cumulative amount of Li+ that was washed out accounted for 92.61%, 82.07% and 75.25% of the injection volume in three waste columns (1#, 2# and 3#) with landfill densities of 497.5, 726.4 and 970.1 kg m-3 at the thirtieth recirculation, respectively. The results revealed that a greater landfill density yielded a smaller amount of Li+ that was washed out per recirculation cycle and the cumulative amount of Li+ washed out, and a longer contact time between the waste and leachate. Moreover, waste columns 1#, 2# and 3# are reactors with a high dispersion and obvious retention zones, and their Morrill Dispersion Index (MDI) values were 25.00, 34.51 and 24.55, respectively. A short-flow phenomenon is obvious in the reactor with a low landfill density. Furthermore, the plug-flow effect is relatively better in the reactor with a high landfill density. To achieve a uniform distribution of recirculated leachate in the landfill, the MDI of the reactor should be reduced combined with other measures, such as pre-crushing and different recirculation schemes.

Long Term Effects of Dialysis Adequacy, Residual Renal Function, Nutritional Indices on CAPD Patient Outcome / 대한신장학회잡지

PURPOSE: Several factors including dialysis adequacy are now known to be related to clinical outcomes of CAPD patients. In our study, the long term effects of dialysis adequacy, residual renal function, nutritional indices, and peritoneal membrane transport characteristics on the outcomes of CAPD patients were evaluated. METHODS: Prevalent or incident 127 patients were enrolled from February 1998 to January 1999. Follow-up was terminated in January 2003. In 41 patients, parameters of adequacy were reevaluated, and the effects of parameter change over time on patient outcomes were analyzed. RESULTS: Seventy-two were male. Twenty-nine (23%) were diabetic. Mean age was 47+/-2.9 years, and the mean follow up period was 45+/-.8 months. The baseline serum albumin was 3.7+/-.5 g/dL. nPCR was 0.8+/-.2 g/kg/d, and %lean body mass was 68.4+/-4.3. Kt/V was 2.0+/-.7, and Ccr was 64.5+/-8.8 L/wk/1.73 m2. The estimated GFR was 1.1+/-.3 mL/min. The multivariated analysis demonstrated that diabetes, serum albumin, and the patent residual renal function were independent factors of the patient and technique survival. Membrane transport characteristic was a predictor of technique survival. Among patients for whom the parameters of adequacy were reevaluated, a more rapid decrease of serum albumin and a more rapid increase of membrane transport characteristics were associated with increased risk of either death or technique failure. CONCIUSION: Nutritional indices and presence of residual renal function have a significant impact on the clinical outcome. The decrease of serum albumin and the increase of membrane transport characteristic have negative impacts on patient and technique survival.

Long Term Effects of Dialysis Adequacy, Residual Renal Function, Nutritional Indices on CAPD Patient Outcome / 대한신장학회잡지

PURPOSE: Several factors including dialysis adequacy are now known to be related to clinical outcomes of CAPD patients. In our study, the long term effects of dialysis adequacy, residual renal function, nutritional indices, and peritoneal membrane transport characteristics on the outcomes of CAPD patients were evaluated. METHODS: Prevalent or incident 127 patients were enrolled from February 1998 to January 1999. Follow-up was terminated in January 2003. In 41 patients, parameters of adequacy were reevaluated, and the effects of parameter change over time on patient outcomes were analyzed. RESULTS: Seventy-two were male. Twenty-nine (23%) were diabetic. Mean age was 47+/-2.9 years, and the mean follow up period was 45+/-.8 months. The baseline serum albumin was 3.7+/-.5 g/dL. nPCR was 0.8+/-.2 g/kg/d, and %lean body mass was 68.4+/-4.3. Kt/V was 2.0+/-.7, and Ccr was 64.5+/-8.8 L/wk/1.73 m2. The estimated GFR was 1.1+/-.3 mL/min. The multivariated analysis demonstrated that diabetes, serum albumin, and the patent residual renal function were independent factors of the patient and technique survival. Membrane transport characteristic was a predictor of technique survival. Among patients for whom the parameters of adequacy were reevaluated, a more rapid decrease of serum albumin and a more rapid increase of membrane transport characteristics were associated with increased risk of either death or technique failure. CONCIUSION: Nutritional indices and presence of residual renal function have a significant impact on the clinical outcome. The decrease of serum albumin and the increase of membrane transport characteristic have negative impacts on patient and technique survival.